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This laboratory has started since 2013.
Our mission is to uncover the mechanisms of neurodegenerative disorder, including amyotrophic lateral sclerosis (ALS) and Alzheimer's disease (AD) to develop the viable therapy.

2024 Apr. / Dr. Shinno, Ms. Noda, and Ms. Kato joined to our lab.

2024 Apr. / We reported that Dimetyl fumarate activates Nrf2 pathway in glial cells to reduce neuroinflammation in Alzheimer's disease model mice in Journal of Neuroinflammation.

2024 Mar. / Dr. Hashimoto was awarded Ph.D. in medicine, Ms. Yanagisawa was awarded a master degree in medical sciences.

2024 Feb. / We reported that variation of microglial activation derived from genetic backgrounds affects ALS progression in ALS in iScience.

2023 Nov. / We reported that collapse of ER-mito contact site (MAM) induces TBK1 inactivation, resulting in deregulated stress response in ALS in PNAS.

2023 Aug. / We reported that TDP-43 monomerization is a key mechanism of TDP-43 pathology in ALS in Sci Adv.

2023 May / We reported a species-specific aggregation mechanism of canine SOD1 in J Biol Chem.

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Our Recent Activity

2024/8/5

NEW AWARD Dr. Endo and Dr. Oiwa won the Japan Neuroscience Society Young Investigator Award (to F.E.) and Toshihiko Tokizane Memorial Award for Excellent Graduate Study in Neuroscience (to K.O.) in Neuro2024, respectively.

At the awards' ceremony. Prof. Masahisa Katsuno (Dept Neurol, Grad Sch of Medicine, Nagoya Univ), Dr. Endo, Dr. Oiwa, and Prof. Yamanaka from the left.

2024/4/1

NEW Dr. Kanako Shinno (Designated Assistant Prof.), Ms. Aki Noda (D1), and Ms. Miku Kato (B2) joined to our lab.

Our group photo taken in Apr. 2024.

2024/4/1

NEW Prof. Yamanaka was appointed vince president (research) of Nagoya University.

Governing Structure (President & Vince Presidents)

2024/4/1

RESEARCH Our work is now open in Journal of Neuroinflammation:

Our study revealed that dimethyl fumarate (DMF), a clinically used drug to activate the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, attenuated neuroinflammation, particularly in astrocytes, and reversed cognitive dysfunction presumably by activating the Nrf2-dependent pathway in Alzheimer's disease (AD) model mice. Our study shows a possibility of DMF repositioning as a drug for AD treatment.

Open Access
Wang T, Sobue A, Watanabe S, Komine O, Saido TC, Saito T, Yamanaka K
"Dimethyl fumarate improves cognitive impairment and neuroinflammation in mice with Alzheimer’s disease."
Journal of Neuroinflammation (2024) 21(1), 55.

2024/3/25

NEW Dr. Hashimoto was awarded Ph.D. in medicine, Ms. Yanagisawa was awarded a master degree in medical sciences, respectively.

Taken in our Lab. Ms. Yanagisawa, Prof. Yamanaka, and, Dr. Hashimoto from the left.

The thesis of Dr. Hashimoto is based on the article publised in Journal of Biological Chemistry as below.

Open Access
Hashimoto K, Watanabe S, Akutu M, Mukai N, Kamishina H, Furukawa Y, Yamanaka K
"Intrinsic structural vulnerability in the hydrophobic core induces species-specific aggregation of canine SOD1 with degenerative myelopathy–linked E40K mutation"
J Biol Chem (2023) 299(6): 104798. DOI: 10.1016/j.jbc.2023.104798.

Press release from Nagoya Univ.

2024/2/6

NEW Dr. Oiwa recieved a Ph.D. in medical sciences.

The thesis is based on the article publised in Science Advances as below.

Open Access
Oiwa K, Watanabe S, Onodera K, Iguchi Y, Kinoshita Y, Komine O, Sobue A, Okada Y, Katsuno M, Yamanaka K
"Monomerization of TDP-43 is a key determinant for inducing TDP-43 pathology in amyotrophic lateral sclerosis."
Sci Adv (2023) 9(31): eadf6895. DOI: 10.1126/sciadv.adf6895.

Press release from Nagoya Univ.

2024/2/1

RESEARCH Our work is now open in iScience :

Genetic background variation impacts microglial heterogeneity, especially disease-associated microglia (DAM), to affect the disease progression in ALS. In a Balb strain, neuroprotective DAM was less induced than a B6(J) strain, resulting in reduced production of insulin-like growth factor-1 (IGF-1) and macrophage colony-stimulating factor (M-CSF). Targeting the reactivity of microglia may be a future therapeutic stratgey for ALS.

Open Access
Komine O, Ohnuma S, Hinohara K, Hara Y, Shimada M, Akashi T, Watanabe S, Sobue A, Kawade N, Ogi T, Yamanaka K
"Genetic background variation impacts microglial heterogeneity and disease progression in amyotrophic lateral sclerosis model mice."
iScience (2024) 27(2), 108872.

Press release from Nagoya Univ.

2024/2/1

MEETING Prof. Yamanaka gave an special lecture in the 8th Winter School of the Japanese Society of Osteoimmunology, the 1st International Conference on Neuroscience & Osetoimmunology (Feb. 1st, Nagano, Japan).

2023/12/7

MEETING We gave presentations of our study as follows:

・ Dr. Watanabe: Poster presentation in 34th International Symposium on ALS/MND (Barsel, Switzerland)

・ Prof. Yamanaka: Special lecture entitled "Molecular basis of TDP-43 pathology in ALS" in The 46th Japan Association of Neural Tissue Culture (Kanagawa, Japan)
・ Prof. Yamanaka gave a talk in syposium in the 35th Annual Meeting of the Japanese Society for Neuroimmunology (Sep. 14th, Tokyo, Japan).
・ Prof. Yamanaka gave an invited lecture in the 7th ALS Cafe (Oct. 7th, online hosted by Toho University).

2023/11/27

MEETING We gave presentations as follows in The 42nd Annual Meeting of Japan Society for Dementia Research (11/24〜26, Nara Prefectural Convention Center)

・Dr. Komine, Dr. Kawade, and Ms. Maekawa: poster presentation.
・Prof. Yamanaka and Dr. Sobue: Talk in the symposium.

2023/11/16

RESEARCH Our work is now open in Proceedings of the National Academy of Sciences :

We found that disruption of the mitochondria-associated membranes (MAMs) in Amyotrophic Lateral Sclerosis (ALS) iactivates TANK-binding kinase 1 (TBK1), one of the ALS causative gene products. The TBK1 inactivation resulted in impaired cellular stress response leading to cell death in vitro and motor dysfunction in vivo. Thus, MAM-TBK1 axis may be a promising target for a future ALS therapy.

Open Access
Watanabe S, Murata Y, Oka Y, Oiwa K, Horiuchi M, Iguchi Y, Komine O, Sobue A, Okada Y, Katsuno M, Ogi T, Yamanaka K
"Mitochondria-associated membrane collapse impairs TBK1-mediated proteostatic stress response in ALS."
Proc Natl Acad Sci USA (2023) 120(47): e2315347120. DOI: 10.1073/pnas.2315347120.

Press release from Nagoya Univ.

2023/10/1

Mr. Yokoi and Ms. Mastui have joined to our lab.

2023/8/4

RESEARCH Our paper is now open in Science Advances :

We found that TDP-43 dimerization/multimerization is impaired in the postmortem brains and spinal cords of patients with sporadic amyotrophic lateral sclerosis (ALS). Expression of N-terminal dimerization-deficient mutant TDP-43 in Neuro2a cells and induced pluripotent stem cell-derived motor neurons recapitulates TDP-43 pathology. Moreover, TDP-DiLuc, a novel reporter assay to evaluate TDP-43 dimerization/multimerization, could detect decreased N-terminal dimerization of TDP-43 prior to the TDP-43 pathological changes. Our findings may be important in future research on early pathogenic events related to TDP-43 and in the search for early diagnostic markers or therapeutic strategies for ALS.

Open Access
Oiwa K, Watanabe S, Onodera K, Iguchi Y, Kinoshita Y, KOmine O, Sobue A, Okada Y, Katsuno M, Yamanaka K
"Monomerization of TDP-43 is a key determinant for inducing TDP-43 pathology in amyotrophic lateral sclerosis."
Sci Adv (2023) 9(31): eadf6895. DOI: 10.1126/sciadv.adf6895.

Press release from Nagoya Univ.

2023/7/9

MEETING We gave presentations of our studies in The 46th Annual Meeting of the Japan Neuroscience Society (Aug 1st - 4th, Sendai).

・ Mr. Sakai, Ms. Wang, Ms. Maekawa, Ms. Yanagisawa, Drs. Komine, Watanabe, Sobue, Kawade, and Shimohata: Poster presentations
・ Dr. Horiuchi: Training School for Next Generation Scientists (Oral & Poster presentations)
・ Dr. Endo gave an presentation in the symposium.
・ Prof. Yamanaka co-chaired the session, "Amyotrophic Lateral Sclerosis", with Prof. Dr. Yoshitaka Nagai (Dept of Neurology, Kindai University).

2023/7/18

Dr. Fumito Endo has been back to our lab as Lecturer from UCLA.

2023/7/9

MEETING Our member gave presentations in The 66th Annual Meeting of the Japanese Society for Neurochemistry, The 64th Annual Meeting of the Japanese Society of Neuropathology: Joint Meeting (July 6th - 8th, Kobe) as below:

・ Mr. Sakai, Dr. Horiuchi - Poster presentations
・ Dr. Watanabe: Talk in the symposium
・ Prof. Yamanaka: Co-organized the symposium entitled as "Neurology and Psychiatry research from the viewpoint of neuroinflammation, immunology, and pathology." with Dr. Izumi Kawachi (Associate Professor, Niigata University).

2023/6/29

Prof. Yamanaka has been appointed President of the Japan Neuroscience Society.

Message from the President (Japan Neurosicence Society)

2023/6/17

RESEARCH Our review article on lipid metabolism in AD is now open in FEBS Open Bio

Open Access
Kawade N & Yamanaka K
"Novel insights into brain lipid metabolism in Alzheimer's disease: Oligodendrocytes and white matter abnormalities"
FEBS Open Bio (2023) Epub ahead of print DOI: 10.1002/2211-5463.13661.

2023/5/22

RESEARCH Our paper is now open in Journal of Biological Chemistry

E40K mutation induces aggregation in canine SOD1, but not human SOD1; However, the mechanism remains unknown. We found that the species-specific aggregation depended on a difference of the 117th amino acid residues, methionine and leucine in canines and humans, respectively. Crystal structural analysis revealed the instability of the hydrophobic core in canine SOD1 because of 117th methionine creating a cavity, but the cavity was filled by 117th leucine. Instability of canine SOD1 due to the cavity is the basis of species-specific aggregation of SOD1, and a clue for developing novel therapeutics for canine DM.

Open Access
Hashimoto K, Watanabe S, Akutu M, Mukai N, Kamishina H, Furukawa Y, Yamanaka K
"Intrinsic structural vulnerability in the hydrophobic core induces species-specific aggregation of canine SOD1 with degenerative myelopathy–linked E40K mutation"
J Biol Chem (2023) 299(6): 104798. DOI: 10.1016/j.jbc.2023.104798.

Press Release from Nagoya University

2023/5/10

RESEARCH Our review article on neuroinflammation in AD is now open in Inflammation & Regeneration

Open Access
Sobue A, Komine O, Yamanaka K
"Neuroinflammation in Alzheimer’s disease: microglial signature and their relevance to disease"
Inflamm Regen (2023) 43: 26. DOI: 10.1186/s41232-023-00277-3.

2023/4/1

Dr. Shimohata joined to our lab. Drs. Komine and Watanabe became lecturers.

Our lab members in 2023.

2022/3/18

MEETING Dr. Komine join as a symposist in the 128th Annual meeing of The Japanese Association og Anatomists (Sendai, Japan).

2023/3/16

MEETINGAWARD Dr. Kawade, Dr. Horiuchi, Ms. Wang, Ms. Maekawa, Mr. Sakai, and Ms. Yanagisawa gave their presentations in 4th CIBoG retreat ( Feb. 18th and 20th, online and Nagoya Univ.). Dr. Horiuchi won the best presentation award.

Prof. Yamanaka and Dr. Horiuchi in our Lab.

2023/2/9

RESEARCH Our invited review article about the role of sex hormones in neuroinflammation in Alzheimer's diseases is now oepn in Clinical & Experimental Neuroimmunology .

Open Access
Maekawa K, Yamanaka K
"Role of sex hormones in neuroinflammation in Alzheimer's disease."
Clin Exp Neuroimmunol (2023) 4:16, 1045647. DOI: 10.1111/cen3.12744.

2023/2/2

RESEARCH Our work is now open in Neurobiology of Disease.

We found that sigma-1 receptor (σ1R), a MAM-specific chaperone like protein, maintained ATAD3A as a monomer to prevent mitochondrial fragmentation in ALS. Targeting σ1R and ATAD3A axis may provide a novel therapeutic approach for ALS.

Open Access
Watanabe S, Horiuchi M, Murata Y, Komine O, Kawade N, Sobue A, Yamanaka K
"Sigma-1 receptor maintains ATAD3A as a monomer to inhibit mitochondrial fragmentation at the mitochondria-associated membrane in amyotrophic lateral sclerosis."
Neurobiol Dis (2023) 2:179, 106031. DOI: 10.1016/j.nbd.2023.106031.

Press release from Nagoya University

2023/1/4

RESEARCH Our work is now open in Frontiers in Cellular Neuroscience.

In this study, we revealed cell type-specific transcriptional alternation from the microarray data of ALS model mouse whole spinal cord. The identified gene set may lead to identify a novel therapeutic target for ALS such as alternations of lipid homeostasis in astrocytes.

Open Access
Yamashita H, Komine O, Fujimori-Tonou, N, Yamanaka K
"Comprehensive expression analysis with cell-type-specific transcriptome in ALS-linked mutant SOD1 mice: Revisiting the active role of glial cells in disease."
Front Cell Neurosci (2023) 4:16, 1045647. DOI: 10.3389/fncel.2022.1045647.

Our Past Activity in 2022

2022/12/3

MEETING Our members gave presentations in the following meetings:

The26th Glia meetings (Dec 3rd, Nagoya Convention Hall)
Prof. Yamanaka organized the meeting, and Dr. Horiuchi gave an oral presentation.

Dr. Sobue. Dr. Kawade, and Ms. Maekawa gave poster presentations in Joint meeting of the 41st annual meeitng of the Japan Dementia and the 37th annual meeting of the Japanese Psychogeratric Society. (Nov 25th – 27th, Tokyo International Forum)

The 95th annual meeting of the Japanese Biochemical Society (Nov 9th – 11th, Nagoya Congress Center)
Prof. Yamanaka co-organized the symposium with Prof. Yoshitaka Nagai (Kinki Univ.).
Dr. Watanabe gave presentation in the symposium.
Mr. Sakai and Mr. Hashimoto gave presentations.

Prof. Yamanaka gave a presentation in the JSNI-PNIRS Asia-Pacific Joint Symposium held in The 34th annual meeting of the Japanese Society for Neuroimmunology (Oct 20th – 21st, Dejima Messe Nagasaki).

Mr. Sakai gave a presentation in The 4th Japan-UK Neuroscience Symposium 2022 (Sep 19th – 22nd, Nagano)

Mr. Hashimoto gave a presenttaion in The 165th meeting of the Japanese Society of Veterinary Science (Sep 6th – 8th, virtual meeting)

Dr. Horiuchi, Ms. Maekawa, and Mr. Hashimoto gave presentations in the 12th Joint Symposium of Nagoya University Graduate School of Medicine and National Institute for Physiological Sciences (Sep 10th, virtual meeting)

Prof. Yamanaka gave an invited talk in The 43rd annual meeting of the Japanese Society of Inflamaation and Regeneration (Jul 6th – 7th, Hyogo)

2022/10/1

Mr. Rikuto Sugihara and Ms. Rara Ohashi joined to our lab.

2022/8/20

RESEARCH Our collaborative work is now available on Acta Neurologica Belgica

Open Access
Hirayama T, Shibukawa M, Yanagihashi M, Warita H, Atsuta N, Yamanaka K, Kano O
"Investigation of non-motor symptoms in patients with amyotrophic lateral sclerosis."
Acta Neurol Belg (2022) DOI: 10.1007/s13760-022-02036-6.

2022/7/3

MEETING Our members gave presentation as follows on Neuro 2022 (Joint meeting of the 45th annual meeting of the Japan Neuroscience Society, the 65th annual meeting of the Japanese Society for Neurochemistry, and the 32rd annual conference of the Japanese Neural Network Society) (Jun 30th – Jul 3rd, Okinawa Convention Center).

Prof. Yamanaka co-organized the symposium, "Neuroinflammation and Dimentia, Neurodegenerative diseases", with Prof. Taisuke Tomita (Univ. of Tokyo)
Dr. Komine gave an presentation on the symposium.
Dr. Watanabe, Dr. Horiuchi, Mr. Hashimoto gave oral presentations.
Dr. Sobue, Dr. Kawade, Ms. Maekawa, Ms. Shimogawa, Ms. Wang, and Mr. Sakai gave poster presentations.

2022/6/1

MEETING Prof. Yamanaka, Dr. Sobue, and Dr. Oiwa gave presentations in 63rd Annual Meeting of the Japanese Society of Neurology (May 18th – 21st, Tokyo). Dr. Oiwa won a best presentation award.

・Symposium presentations: Drs. Yamanaka and Sobue
・Oral presentation: Dr. Oiwa

2022/4/1

Ms. Yanagisawa has joined to our Lab.

A group photo taken in Higashiyama Campus in Apr. 2022.

2022/4/1

Mr. Sakai and Dr. Hashimoto became JSPS Research Fellows (Mr. Sakai DC1, Dr. Hashimoto DC2).

2022/2/19

MEETINGAWARD Dr. Horiuchi, Ms. Wang, Ms. Shimogawa, Dr. Hashimoto, Ms. Maekawa, and Mr. Sakai gave a presentation in 3rd CIBoG retreat (14th NAGOYA global retreat) (Feb. 19th, online). Dr. Hashimoto won the presentation award.

Prof. Yamanaka and Dr. Hashimoto in our Lab.

Our Past Activity in 2021

2021/11/28

MEETING Dr. Yamanaka co-organized a symposium entitled "Inflamattion, microglia and dementia" with Dr. Naruhiko Sahata (National Institutes for Quantum Science and Technology), and Dr. Sobue and Ms. Maekawa gave presentations in The 40th Annual Meeting of Japan Society for Dementia Research (Nov. 26-28th, 2021 at Tokyo International Forum and online).

2021/11/25

AWARD Dr. Hashimoto won the presentation awards in the 164th Anuual meeting of the Japanese Society of Veterinary Science and the 94th Annual Meeting of the Japanese Biochemical Society.

Prof. Yamanaka and Dr. Hashimoto in our Lab.

2021/11/25

AWARDGRANT Ms. Maekawa became an Interdisciplinary Frontier Fellow of Nagoya University. Dr. Hashimoto and Ms. SHimogawa became an Interdisciplinary Frontier Next Generation Researcher of Tokai National Higher Education and Research System (THERS).

2021/11/25

MEETING We gave presentations of our studies and organized symposiums as bellow:

The 44th Annual Meeting of the Japan Neuroscience Society, joined with the 1st China-Japan-Korea (CJK) International Meeting (Jul. 28-31, Kobe Convention Center and online)
Drs. Komine, Sobue, Watanabe, Oiwa, Horiuchi, Ms. Wang, and Mr. Sakai gave presentations.

Pan-Asia Consortium for Treatment & Research (PACTALS) 2021 (9/17-18, online)
Prof. Yamanaka talked and chaired the symposium.
Drs. Watanabe, Horiuchi, Hashimoto, and Mr. Sakai gave presentations.

Dr. Hashimoto gave an presentation in the 164th Anuual meeting of the Japanese Society of Veterinary Science .

The 33rd Annual Meeting of the Japanese Society for Neuroimmunology （10/21-22, online）
Prof. Yamanaka co-chaired a symposium entitled "Advances in basic research on molecular pathology of neurological diseases" with Prof. Mineki Saito (Kawasaki Medicai Univ.).
Dr. Komine gave an presentation.

Prof. Yamanaka gave an invited talk in the 74th Anuual Meeting of the Japan Society of Neurovegetative Research (10/23, online).

Prof. Yamanaka gave an presentation as a symposist in the 39th Anuual Meeting of Japanese Society of Neurological Therapeutics (10/28, Tsu, Mie).

the 94th Annual Meeting of the Japanese Biochemical Society (11/3-5, online)
Drs. Watanabe, and Hashimoto gave presentations.

2021/10/1

Ms. Maika Kato joined to our Lab.

2021/6/24

NEWRESEARCH Our paper is now open in The FASEB Journal.

The mitochondria-associated membrane (MAM) is a functional subdomain of the endoplasmic reticulum membrane that tethers to the mitochondrial outer membrane and is essential for cellular homeostasis. However, it is still uncertain whether MAM disruption is a common pathology in ALS, mainly due to the absence of a simple, quantitative tool for monitoring the status of MAM. In this study, to examine the effects of various ALS-causative genes on MAM, we created the following two novel MAM reporters: MAMtracker-Luc and MAMtracker-Green. We suggest that MAM disruption is a common pathological feature in ALS using the MAMtrackers. Furthermore, we anticipate our MAMtrackers, which are suitable for high-throughput assays, to be valuable tools to understand MAM dynamics.

Open Access
Sakai S, Watanabe S, Komine O, Sobue A, and Yamanaka K
Novel reporters of mitochondria-associated membranes (MAM), MAMtrackers, demonstrate MAM disruption as a common pathological feature in amyotrophic lateral sclerosis.
The FASEB Journal (2021) e21688. DOI: 10.1096/fj.202100137R

2021/4/1

Dr. Kawade (Assistant Professor) and Ms. Nagata (Technical Staff) joined to our lab.

Our Lab Group Photo in 2021.

2021/2/6

MEETING Ms. Horiuchi, Mr. Hashimoto, Ms. Maekawa and Mr. Sakai gave presentations in 2nd CIBoG retreat/13th Nagoya Global retreat(Feb 6th, online). Ms. Maekawa won a best poster presentation award in the meeting.

In our Lab. Dr. Yamanaka, Ms. Maekawa and Dr. Sobue from the right.

2021/2/1

RESEARCH Our work is now open in Acta Neuropathologica Communications:

In this study, we analyzed gene expression profiles of microglia isolated by magnetic activated cell sorting (MACS) from three mouse models for neurodegenerative diseases: AppNL-G-F/NL-G-F mice that display an amyloid pathology, rTg4510 mice with tauopathy, and SOD1(G93A) mice with motor neurodegeneration by RNA-sequencing. Despite robust neuroinflammation with microglial responses in all mouse models, AppNL-G-F/NL-G-F mice do not show neuronal death, whereas rTg4510 and SOD1(G93A) mice show a substantial loss of neurons. We found that the reduction of homeostatic microglial genes was correlated with severity of neurodegeneration, whereas DAM genes were uniformly upregulated in all mouse models. Moreover, in human precuneus with early AD pathology, reduced gene expressions of microglia and oligodendrocytes were observed, although DAM genes were not upregulated. Results from the present study indicate a correlation between glial phenotypes and severity of neurodegeneration, and also provide important resources to better understand the role of glial dysfunction in progression of Alzheimer's disease.

Open Access
Sobue A, Komine O, Hara Y, Endo F, Mizoguchi H, Watanabe S, Murayama S, Saito T, Saido T, Sahara N, Higuchi M, Ogi T and Yamanaka K
"Microglial gene signature reveals loss of homeostatic microglia associated with neurodegeneration of Alzheimer’s disease."
Acta Neuropathol Commun (2021) 9: 1. DOI: 10.1186/s40478-020-01099-x

Press release from Nagoya Univ

Our Past Activity in 2020

2020/11/28

MEETING Dr. Sobue won an oral presentation award in the 39th Annual Meeting of Japan Society for Dementia Research (11/26-28, Online and Nagoya International Conference Center).
Prof. Yamanaka co-organized a symposium entitled as "Neuroinflammation in Alzheimer's disease" with Prof. Ikuo Tooyama (Shiga University of Medical Science). Ms. Wang and Ms. Shimogawa also gave poster presentations in the meeting.

Dr. Sobue (left), who won the prize, and Prof. Dr. Yamanaka (right).

2020/11/28

RESEARCH Our collaborative work is now open in Molecular Brain:

Open Access
Saifullah MAB, Komine O, Dong Y, Fukumoto K, Sobue A, Endo F, Saito T, Saido TC, Yamanaka K, Mizoguchi H
"Touchscreen-based location discrimination and paired associate learning tasks detect cognitive impairment at an early stage in an App knock-in mouse model of Alzheimer's disease."
Mol Brain (2020) 13: 147.

Press release from Nagoya Univ.

2020/10/27

RESEARCH Our work is now open in Cell Death & Disease :

We found that microtubule-related proteins (MRPs) and RNA-binding proteins (RBPs) co-aggregated with TDP-43. These two types of proteins sequestered TDP-43 through independent mechanisms; a liquid-liquid phase separation (LLPS) and an aggresome formation. Moreover, in sporadic ALS patients, approximately half of skein-like TDP-43 inclusions were co-localized with HDAC6, but round and granular type inclusion were not. Our findings suggest that two pathways (LLPS and aggresomes) independently induce TDP-43 aggregation and that both the mechanisms are involved in TDP-43 pathology in sporadic ALS patients. The findings will lead to a novel therapeutic strategy for ALS.

Watanabe S, Inami H, Oiwa K, Murata Y, Sakai S, Komine O, Sobue A, Iguchi Y, Katsuno M, Yamanaka K
"Aggresome formation and liquid–liquid phase separation independently induce cytoplasmic aggregation of TAR DNA-binding protein 43."
Cell Death Dis (2020) 11: 909. DOI: 10.1038/s41419-020-03116-2

Press release from Nagoya Univ.

2020/10/27

MEETING We gave presentations in the symposiums/conferences listed below:

The 43rd Annual Meeting of the Japan Neuroscience Society （7/29-8/1, Online Meeting）
・Prof. Yamanaka co-organized the symposium: "Infrastructures of the brain that support logistics solutions in health and disease" with Dr. Yu Hayashi (WPI-IIIS, Tsukuba Univ.).
・Drs. Komine, Sobue, and Watanabe gave oral/poster presentations.

61st Annual Meeting of the Japanese Society of Neurology （8/31-9/2, Okayama Convention Center and Online Meeting）
・Prof. Yamanaka gave an presentation in the symposium.
・Dr. Oiwa gave an presentation.

The 63rd Annual Meeting of the Japanese Society for Neurochemistry （9/10-9/12, Online Meeting）
・Prof. Yamanaka co-organized the symposium with Dr. Minako Ito (Kyusyu Univ.) and gave an presentation as a symposiast.

The 93rd Annual Meeting of the Japanese Biochemical Society （9/14-9/16, Online Meeting）
・Prof. Yamanaka co-organized the symposium: "Brain Infrastructure: A new logistic system of the brain in health and disease." with Dr. Kaoru Yamada (Univ. Tokyo).
・Drs. Komine and Watanabe gave presentations as symposiasts.

The 32nd Annual Meeting of the Japanese Society for Neurochemistry （10/1-10/2, Online Meeting）
・Prof. Yamanaka co-chaired the symposium: "microglia: frontiers in clinical and basic research" with Dr. Hideyuki Takeuchi (Yokohama City Univ.) and gave an presentation.

2020/10/1

Mr. Sakakibara and Ms. Kinoshita (both B3) joined in our laboratory.

2020/9/23

RESEARCH Our collaborative work with Kiyama Lab. is now open in EMBO journal :

Konishi H., Okamoto T., Hara Y., Komine O., Tamada H., Maeda M., Osako F., Kobayashi M., Nishiyama A., Kataoka Y., Takai T., Udagawa N., Jung S., Ozato K., Tamura T., Tsuda M., Yamanaka K., Ogi T., Sato K., Kiyama H.
"Astrocytic phagocytosis is a compensatory mechanism for microglial dysfunction."
EMBO J (2020) 22: e104464. DOI: 10.15252/embj.2020104464

2020/8/28

RESEARCH Our collaborative work with Dr. Hasnain's team in Univ. Liverpool in EBioMedicine :

A group of researchers from the Universities of Liverpool (UK) and Nagoya (Japan) have shown that a Selenium based drug-molecule called ebselen and a number of other novel compounds developed at Liverpool can change many of the toxic characteristics of a protein, superoxide dismutase (SOD1), which causes some cases of ALS, also known as motor neuron disease as well as Lou Gehrig’s disease.

Amporndanai K, Rogers M, Watanabe S, Yamanaka K, O’Neill P. M., Hasnain S. S.
"Novel Selenium-based compounds with therapeutic potential for SOD1-linked Amyotrophic Lateral Sclerosis."
EBioMed (2020) 59: 102980. DOI: 10.1016/j.ebiom.2020.102980

Press release from Nagoya Univ.

2020/4/1

RESEARCH Our collaborative works are now open in Neurochem Int and Cell:

Sugiyama M, Banno R, Yaginuma H, Taki K, Mizoguchi A, Tsunekawa T, Onoue T, Takagi H, Ito Y, Iwama S, Goto M, Suga H, Komine O, Yamanaka K, Arima H.
"Hypothalamic glial cells isolated by MACS reveal that microglia and astrocytes induce hypothalamic inflammation via different processes under high-fat diet conditions."
Neurochem Int (2020) 136: 104733. DOI: 10.1016/j.neuint.2020.104733

Nakazawa Y, Hara Y, Oka Y, Komine O, van den Heuvel D, Guo C, Daigaku Y, Isono M, He Y, Shimada M, Kato K, Jia N, Hashimoto S, Kotani Y, Miyoshi Y, Tanaka M, Sobue A, Mitsutake N, Suganami T, Masuda A, Ohno K, Nakada S, Mashimo T, Yamanaka K, Luijsterburg MS, Ogi T
"Ubiquitination of DNA Damage-Stalled RNAPII Promotes Transcription-Coupled Repair."
Cell (2020) 180(6): 1228-1244.e24. DOI: 10.1016/j.cell.2020.02.010

2020/4/1

Dr. Hashimoto & Ms. Maekawa have joined our lab.

Our Lab members in 2020.

2020/1/24

RESEARCHOur paper is now open in Molecular Brain.

TDP-43 is a key molecule in ALS pathology. Transgenic mice models of TDP-43 suffer from acute toxicity induced by excess amounts of TDP-43 proteins. Therefore, we established TDP-43(M337V) knock-in mice by genome editing using Cas9 (A). The knock-in mice showed RNA deregulation dependent on TDP-43 gain-of-function mechanism (B), similar to the previous studies (White et al. (2018) Nat Neurosci etc.), but no motor neuron degeneration was observed (C). These results suggest that additional conformational change of TDP-43 protein may be needed to develop TDP-43 pathology.

Open Access
Watanabe S, Oiwa K, Murata Y, Komine O, Sobue A, Endo F, Takahashi E and Yamanaka K
"ALS-linked TDP-43M337V knock-in mice exhibit splicing deregulation without neurodegeneration."
Molecular Brain (2020) 13: 8. DOI: 10.1186/s13041-020-0550-4

2020/1/24

MEETINGWe gave presentations in the meetings listed below:

・Dr. Sobue: 2019 Nov The 38th Annual Meeting of Japan Society for Dementia Research
・Prof. Yamanaka, Dr. Watanabe: 2019 Dec 30th International Symposium on ALS/MND (Perth, Australia)

Our Past Activity in 2019

2019/10/1

Ms. Yuri Banno and Chitose Imai have joined to our Lab as students of Training for Medical Research in 2019.

2019 Oct / Welcome party at our lab.

2019/7/31

RESEARCHOur paper is now open in Acta Neuropathologica Communications.

We investigated the pathological role of TDP-43 N-terminal fragments, which is also accumulated in ALS patients as well as full-length TDP-43 and TDP-43 C-terminal fragments. We produced TDP-ΔC knock-in mice, expressing TDP-43 N-terminal fragments at the similar level of endogenous TDP-43 (left panel). This mice showed age-dependent motor dysfunction (right panel) with reduced C-boutons, large cholinergic synapses on motor neurons, and Notch1-Akt signaling pathway (middle panel, arrowheads indicate C-boutons). Our data uncovered a detrimental role of N-terminal TDP-43 fragments in ALS pathology in mice, associated with suppression of Akt surviving signal.

Open Access
Nishino K, Watanabe S, Shijie J, Murata Y, Oiwa K, Komine O, Endo F, Tsuiji H, Abe M, Sakimura K, Mishra A, Yamanaka K
"Mice deficient in the C-terminal domain of TAR DNA-binding protein 43 develop age-dependent motor dysfunction associated with impaired Notch1-Akt signaling pathway."
Acta Neuropathologica Communications (2019) 7(1): 118. DOI: 10.1186/s40478-019-0776-5

2019/7/31

MEETING Prof. Yamanaka, Drs. Komine, Sobue, Watanabe, and Oiwa gave their presentations in Neuro 2019 （2019/7/25-28, Niigata）.

2019/5/28

MEETING Prof. Yamanaka & Dr. Watanabe gave presentations in a metting of Grant-in-Aid for Scientific Research on Innovative Areas: “Toward an integrative understanding of functional zones in organelles” (May 27, 28 in Osaka University).

2019/5/24

MEETING Prof. Yamanaka gave a presentation in the 60th annual meeting of the Japanese Society of Neurology (May 22-25 in Osaka).

2019/4/1

Three new graduate students have joined to our Lab: Mr. Sakai (M1), Ms. Shimogawa (D1), and Dr. Horiuchi (MD, D1).

Group photo of our current laboratory members (2019 Apr in Higashi-yama Campus, Nagoya University).

2019/2/12

MEETING Dr. Watanabe gave a presentation in Japan-UK Neuroscience Symposium organized by AMED, Japan (Kisarazu, Chiba).

2019/2/8

MEETING Dr. Komine gave a presentation in the 1st RIEM Symposium.

2019/2/1

Ms. Miyoshi has joined to our lab as a Technical Staff.

Our Past Activity in 2018

2018/12/7

MEETING Prof. Yamanaka & Dr. Watanabe gave presentations in the 29th International Symposium on ALS/MND (Glasgow, UK).

2018/12/1

MEETING Prof. Yamanaka, Dr. Komine, and Dr. Sobue gave presentations in 23rd Glia meetings (Prof. Yamanaka talked as an invited speaker).

2018/12/1

Ms. Banno, an undergraduate student (B1), has joined to our lab.

2018/11/7

MEETING Prof. Yamanaka & Dr. Komine gave presentations in Neuroscience 2018 (San-Diego, CA, USA).

2018/10/4

MEETING Dr. Sobue gave a presentation in 37th Annual Meeting of Japan Society for Dementia Research (Oct 12-14 in Sapporo).

2018/10/1

Mr. Iida & Mr. Natsume have joined to our lab in Basic Science Sminar. In addition, Ms. Wang has joined to our lab as a research student.

Group Photo at the welcome party.

2018/9/12

Mr. Sugiyama & Ms. Kinoshita joined to our laboratory couse.

At our laboratory. Dr. Watanabe, Ms. Kinoshita, Mr. Sugiyama, and Prof. Yamanaka from the left.

2018/9/12

MEETING Prof. Yamanaka, Dr. Watanabe, and Mr. Inami gave presentations in the 61st Annual Meeting of the Japanese Society for Neurochemistry (Sep 6-8, Kobe).

Prof. Yamanaka (left) and Mr. Inami (right) in the poster session floor.

2018/9/12

PRESS Dr. Yamanaka got an interview on Council of Research Institute and Centers of Japanese National Universities.

2018/7/30

MEETING Drs. Watanabe, Komine, and Sobue gave presentations in the 41st Annual Meeting of the Japan Neuroscience Society (Jul 26-30, Kobe).

2018/7/30

MEETING Prof. Yamanaka talked as an invited speaker in Summer Lecture of Neurology in Niigata (Niigata University).

2018/5/25

MEETING Prof. Yamanaka gave a presentation and organized a symposium in the 59th Annual Meeting of the Japanese Society of Neurology (May 23-26, Sapporo).

2018/5/17

AWARD Mr. Inami won a Medical Student Research Award of Nagoya University 2018.

2018/4/6

RESEARCH Our paper is now open in Cell Death & Differentiation.

We reported that innate immune TRIF pathway plays an important role in protecting a microenvironment surrounding motor neurons by eliminating aberrantly activated astrocytes.

Open Access
Komine O, Yamashita H, Fujimori-Tonou N, Koike M, Jin S, Moriwaki Y, Endo F, Watanabe S, Uematsu S, Akira S, Uchiyama Y, Takahashi R, Misawa H, Yamanaka K
"Innate immune adaptor TRIF deficiency accelerates disease progression of ALS mice with accumulation of aberrantly activated astrocytes."
Cell Death & Differentiation in press doi:10.1038/s41418-018-0098-3.

2018/4/6

Dr. Sobue has joined to our lab as an assistant professor.

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